Abstract This revised K24 will enable me to optimize HIV prevention among opioid-dependent persons through three broad and interrelated aims that include: (1) Mentoring a greater number of new patient-oriented researchers via UConn?s Institute for Collaboration on Health, Intervention, and Policy (InCHIP) and the Yale AIDS Program, (2) Expanding my patient-oriented research (POR) program to include several high priority domestic (e.g., rural West Virginia/Ohio) and international settings (e.g., Uganda, Malaysia, and Ukraine), and (3) Engaging in structured training on critical issues surrounding the implementation of evidence-based HIV prevention within clinical settings nationally and internationally that will complement my POR skill set. The volatile opioid epidemic in the U.S. has taken an unimaginable toll, with 2.1 million Americans having an opioid use disorder (OUD) and overdose deaths reaching 70,200 in 2017 alone, representing over a 400% increase in 15 years.1 In parallel, a number of HIV outbreaks among people who inject drugs (PWID)2 reversed a downward trend in this group,1 reflecting the need to more effectively prevent HIV in this group, especially as patients with OUD transition from prescription pain killers to injectable opioids.3 Consequently, the CDC has intensified efforts to reduce the number of new HIV infections by more effectively and efficiently targeting PWID via: 1) reduced HIV risk behaviors, 2) increased adherence and retention in treatment; and 3) promotion of health behaviors that benefit individual and public health. Although drug- and sex-related HIV risk reduction and adherence are behaviors that are readily modifiable, interventions must be carefully designed and situated in a range of patient-oriented settings in the US and internationally.4-8 I am in the process of expanding my POR to focus on better identifying, understanding, and developing strategies at multiple levels to accommodate such patients so that they can derive optimal HIV prevention benefits via the next generation of interventions (e.g., mHealth).9 Such strategies will need to reinforce adherence to PrEP and other biomedical prevention (e.g., opioid agonist therapies [OAT] and syringe services programs [SSP]) alongside behavioral risk reduction. This will be especially important as priority domestic and international communities struggle with their inability to overcome policy factors that limit or restrict access to the full toolkit of HIV prevention (i.e., PrEP, OAT, SSP, behavioral interventions) for PWID. My ongoing (R01DA044867; Gilead ISR-US-19-10641), recently completed (R01DA032290; R01DA022122), and future HIV prevention projects form the basis of my POR and mentoring program as well as future domestic and international research collaborations. Each of the aims will provide a wide range of opportunities for expanding my POR and for my mentees to develop the skill set they need to become the next generation of HIV prevention scientists.